4/29/2010 @ 4:13PM

Dendreon's Clean Bill Of Health

One of the most controversial biotechnology companies of the past decade is poised to become one of the most successful.

The Food and Drug Administration announced it is approving
Dendreon’s
Provenge, a cell therapy that primes patients’ immune systems to fight off prostate cancer cells. The positive verdict came three years after the agency rejected Provenge in its first attempt at approval. Dendreon did another big study and convinced the agency that its cancer vaccine works.

The approval is a major milestone for Dendreon, the tiny biotechnology company that developed the treatment based on basic research that occurred at Stanford University. Dendreon shares, which have risen more than 200% in the past year, blasted up another 6% to $45 when news of the approval crossed the wire. Then they were halted. When trading restarted, shares were up 31%, to $52.

The FDA approved Provenge for patients whose prostate cancer has spread into their bodies; who have either no symptoms or minimal symptoms from the disease; and who won’t respond to hormone blocking drugs. About 25,000 patients fall into this category each year. The package insert for the medicine, on which Dendreon’s marketing will be based, contains few major warnings about serious side effects (patients get fevers and chills) or caveats about the product’s effectiveness. Provenge will cost $93,000 per course of treatment.

“There’s nothing in any of it that’s a surprise, nothing hidden in the weeds that could dampen the party for Dendreon and prostate cancer patients,” says David Miller of Biotech Stock Research, a longtime Dendreon bull who has recommended the company in his newsletter.

“There will be a large demand for this,” says Mount Sinai School of Medicine urologist Simon Hall, who was involved with several clinical trials of Provenge but has no financial interest in the company. “Patients don’t want chemotherapy. They are looking for alternatives and using your own body to fight cancer is an attractive option.” But he cautioned: “It is not the panacea. You are going to live longer, but eventually the cancer will progress.”

Dendreon had been controversial from the moment it emerged as a cancer-fighting company more than a decade ago, based on research on the immune system that originated with Stanford University researchers. No treatment had ever worked by priming the immune system–Provenge does this by removing cells from the body and priming them. Cell therapies have never worked before either.

In March 2007 an FDA advisory panel voted to approve the drug, based on two studies that had missed their pre-specified main goals but had shown a surprise benefit of increasing survival. But many experts, including some who had served on the panel, doubted this result, fearing it was the result of data dredging.

That May the FDA rejected the drug. Some investors and patient advocates cried foul, holding demonstrations at the FDA’s headquarters to protest the decision.

But last year a larger 512-patient study confirmed the benefit, showing a four-month survival benefit over a placebo treatment.

In the Provenge package insert and in a question and answer document on the FDA website, the agency portrayed this trial as the main reason for Provenge’s approval. In the Q&A the FDA says Provenge was rejected because of doubts that it would be safe and effective, and that those doubts were settled by the large study. Dendreon will have to follow 1,500 patients on Provenge in a registry to try to answer whether or not the treatment causes any elevated risk of stroke, which was a risk in earlier studies.

The controversy isn’t necessarily over. Provenge’s $93,000 price is far higher than Wall Street expected, and the company says it does not expect to be providing discounts. A charity will help patients whose insurers do not cover the treatment.

One unusual aspect of the treatment that has generated controversy is the fact that the vaccine doesn’t shrink the tumor or change the PSA level in most patients. So while the vaccine extends survival in the average patient, an individual has no way of telling if the vaccine is working. “A lot of patients have trouble dealing with this psychologically,” says the urologist Hall. They are used to following ups and downs in their PSA score as a surrogate measure of whether a treatment is working.

In retrospect, “It shouldn’t have been a surprise” that a vaccine would keep people alive longer without killing cancer cells, says Christopher Logothetis of MD Anderson Center in Houston. “The vaccine doesn’t kill cancer cells, it regulates them so the cells are less able to behave aggressively. … The tumor becomes a chronic disease rather than being eradicated.”

Logothetis hopes that Provenge’s approval is only the start. By better understanding how Provenge works on a molecular level, researchers may be able to design better vaccines in the future. “The nation’s investment in research in prostate cancer is now paying off,” he says. “For 50 years we only had one treatment that prolonged survival in prostate cancer [i.e., hormone therapy], and suddenly within a decade we have two.” The other relatively new treatment that works in advanced prostate cancer is the chemotherapy drug taxotere from Sanofi Aventis.

While Provenge is the first therapeutic cancer vaccine approved in the U.S., many more are in development for numerous types of tumors at
Bristol-Myers Squibb
, GlaxoSmithkline and other companies.